PUM1 in Breast Cancer: Tumor Expression and Prognostic and Predictive Significance

Background and Objectives: Breast cancer (BC) is a complex disease requiring a comprehensive treatment approach due to its diverse characteristics. Critical molecular determinants of BC have been identified using advanced genomic, transcriptomic, and proteomic approaches. Assessing the biomarkers associated with the onset of early-stage BC may help identify the risk of metastasis and inform treatment decisions. A previous bioinformatic analysis using two large BC cohorts identified pumilio RNA binding family member 1 (PUM1) as a key gene in invasive BC. However, no study has yet examined the prognostic and predictive value of PUM1 in invasive BC and its correlation with aggressive tumor behavior. This study aimed to fill this need. Materials and Methods: Correlations between PUM1 expression and patients' clinicopathological characteristics and outcomes were explored in publicly available BC transcriptomic data acquired using DNA microarrays (n = 10,872) and RNA sequencing (n = 4421) using BC Gene-Expression Miner v5.0. PUM1 expression in samples from 100 patients with invasive BC at King Abdul Aziz Specialist Hospital, Saudi Arabia, was assessed immunohistochemically. Correlations between PUM1 expression and patients' clinicopathological characteristics (e.g., age, tumor grade, tumor size, and outcome) were assessed. The online platform ROC Plotter was also used to investigate the predictive significance of PUM1. Results: High PUM1 gene and protein expression correlated positively with aggressive features of BC, including high histological grade, high Ki-67 expression, negative hormone receptors, and the triple-negative BC molecular subtype. High PUM1 expression correlated with poor outcomes, and high PUM1 expression was associated with a lower pathological complete response to anti-endocrine treatment but a high response to chemotherapy. Conclusions: These results indicate that PUM1 may serve as a potential prognostic and predictive biomarker in patients with invasive BC. PUM1 may serve as a therapeutic target in BC cases with unfavorable prognoses. However, further validation in larger, multi-center cohorts and further functional assessment are required to deepen our understanding of PUM1's role in BC.